FORMULATION AND EVALUATION OF SOLID-SUPERSATURABLE-SNEDDS OF IBRUTINIB
DOI:
https://doi.org/10.22159/ijap.2022v14i5.45067Keywords:
Ibrutinib, Solubility, L-SNEDDS, Precipitation inhibitor, Magnesium trisilicateAbstract
Objective: The aim of current research is to develop a solid supersaturable self-nanoemulsifying drug delivery system (S-SNEDDS) of ibrutinib for enhancing the solubility and Bioavailability.
Methods: Crossential O 94–Croduret 40SS–carbitol are chosen based on the maximum solubility of ibrutinib and were used to construct ternary phase diagrams with Smix in 3:1 ratio and 70 mg drug loading was done and evaluated for particle size, zeta potential, polydispersity index, entrapment efficiency, drug content and in vitro drug release. Final optimised one is characterised for FTIR, DSC, stability studies and in-vivo studies in rats. To choose a precipitation inhibitor, in vitro precipitation studies were carried out, and supersaturable SNEDDS were made the prepared formulations were evaluated for micromertitic properties and the final optimised one is characterized for FTIR, DSC, SEM and stability studies.
Results: Out of all formulations, F15 exhibited good results with the highest drug release of 98.25% in 60 min. LSS9 with 3% HPMC E4M as the best precipitation inhibitor (PPI) exhibited the smallest droplet size of 65.4 nm, a zeta potential of-17.7 mV, and a PDI of 0.453. SSS1 with magnesium trisilicate as an adsorbent showed best flow characteristics and the highest drug content of 99.72%. The DSC, FT-IR and stability studies confirmed the complexation of ibrutinib and amorphous state of the drug and formulation to be stable for 3 mo. Cmax of the solid supersaturable SNEDDS 139.42±2.16 mg/l was significant (p<0.05) as compared to the pure drug suspension formulation 38.15±1.46 mg/l. Tmax of solid supersaturable SNEDDS formulation and pure drug suspension was 1.00±0.06 h and 1.50±0.02h, respectively. Statistically, AUC of the solid supersaturable SNEDDS formulation was significantly higher (p<0.05) as compared to pure drug suspension formulation.
Conclusion: Thus, this study indicated that the solid SNEDDS could be used as a potential drug carrier for ibrutinib with improved solubility and and bioavailability.
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References
Savale SK. A review-self nanoemulsifying drug delivery system (SNEDDS). Int J Res Pharm Nano Sci. 2015;4(6):385-97.
Reddy, Muthadiandgubbiyappa, Kumar. A comprehensive review on supersaturable self-n anoemulsifying drug delivery system. Asian J Pharm Clin Res. 2021;40-44:10.
Amin A, Ranjana HA. Bruton’s tyrosine kinase inhibitors and their clinical potential in the treatment of B-cell malignancies: focus on ibrutinib. The R Adv Hematol. 2014;5(4):121-33.
Vile gave, Kailash, Vidyasagar, Gali, Chandankar, Pratibha. Preformulation Stud Pharm New Drug Molecule Prod Overview; 2013. p. 1.
Jeevana JB, Sreelakshmi K. Design and evaluation of self-nanoemulsifying drug delivery system of flutamide. J Young Pharm. 2011;3(1):4-8. doi: 10.4103/0975-1483.76413, PMID 21607048.
Sisinthy SP, Rao NK, Sarah CYL. Design, optimization and in vitro characterization of self nano emulsifying drug delivery system of olmesartan medoxomil. Int J Pharm Pharm Sci. 2017 Jan;9(1):94-101. doi: 10.22159/ijpps.2017v9i1.15166.
Dang R. Quality by design-based development of etravirine self microemulsifying drug delivery system. Int J Appl Pharm. 2021;13(3):103-11.
Ujilestari T, Martien R, Ariyadi B, Dono ND, Zuprizal. Self-nanoemulsifying drug delivery system (SNEDDS) of Amomum compactum essential oil: design, formulation, and characterization. J App Pharm Sci. 2018;8(6):14-21. doi: 10.7324/JAPS.2018.8603.
Priani SE, Maulidina SS, Darusman F, Purwanti L, Mulyanti D. Development of self nanoemulsifying drug delivery system for black seed oil (Nigella sativa L.). J Phys.: Conf Ser. 2020;1469(1):012022. doi: 10.1088/1742-6596/1469/1/012022.
Weerapol Y, Limmatvapirat S, Nunthanid J, Sriamornsak P. Self-nanoemulsifying drug delivery system of nifedipine: impact of hydrophilic–lipophilic balance and molecular structure of mixed surfactants. AAPS PharmSciTech. 2014 Apr;15(2):456-64. doi: 10.1208/s12249-014-0078-y, PMID 24452500.
Sanka K, Suda D, Bakshi V. Optimization of solid-self nanoemulsifying drug delivery system for solubility and release profile of clonazepam using simplex lattice design. J Drug Deliv Sci Technol. 2016;33:114-24. doi: 10.1016/j.jddst.2016.04.003.
Balakrishnan P, Lee BJ, Oh DH, Kim JO, Hong MJ, Jee JP. Enhanced oral bioavailability of dexibuprofen by a novel solid self-emulsifying drug delivery system (SEDDS). Eur J Pharm Biopharm. 2009;72(3):539-45. doi: 10.1016/j.ejpb.2009.03.001, PMID 19298857.
Patel PR, Patel KD, Mahajan A. Formulation and evaluation of novel self-nanoemulsifying drug delivery system of sumatriptan succinate. Int J Pharm Sci Res. 2020;11(6):2739-51.
Dash RN, Mohammed H, Humaira T, Reddy AV. Solid supersaturatable self-nanoemulsifying drug delivery systems for improved dissolution, absorption and pharmacodynamic effects of glipizide. J Drug Deliv Sci Technol. 2015;28:28-36. doi: 10.1016/j.jddst.2015.05.004.
Lee DH, Yeom DW, Song YS, Cho HR, Choi YS, Kang MJ. Improved oral absorption of dutasteride via Soluplus®-based supersaturable self-emulsifying drug delivery system (S-SEDDS). Int J Pharm. 2015 Jan 15;478(1):341-7. doi: 10.1016/j.ijpharm.2014.11.060, PMID 25437113.
Subramanian P, Rajnikanth P, Kumar Manish, Kumarappan, Chidambaram. In vitro and in vivo evaluation of supersaturable self-nanoemulsifying drug delivery system (SNEDDS) of dutasteride. Curr Drug Deliv. 2019;16:10.2174.
Reddy BS, Harish G, Ul-Haq Md F. Formulation and in vitro characterisation of solid-self nanoemulsifying drug delivery system (S-SNEDDS) of rilpivirine. Int J Pharm Sci Res. 2016;7(7):3117-29.
Bannow J, Yorulmaz Y, Lobmann K, Müllertz A, Rades T. Improving the drug load and in vitro performance of supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) using polymeric precipitation inhibitors. Int J Pharm. 2020 Feb 15;575:118960. doi: 10.1016/j.ijpharm.2019.118960, PMID 31846728.
Reddy MR, Mishra K, Suresh R. Development and validation of a liquid chromatographic method for the determination of selected anti-cancer drugs in bulk and pharmaceutical formulations. Int J Pharm Res Health Sci. 2018;6(1):2303-7.
Wei LM, Xu ZX, Lv PF, Xue YL, Wang XX, Zhang M. A simp le HPLC method for the determination of ibrutinib in rabbit plasma and its application to a pharmacokinetic study. Lat Am J Pharm. 2016;35:130-4.
Santhoshillendula, Priyanka, Dhandempally, Shirisha V, Knv Rao, Dutt Rajeswar. A new simple method development and validation of ibrutinib in bulk and pharmaceutical dosage form by RP-HPLC. Int J of Pharmacy and Biological Sciences 2019;9(1):36-46.
Prasad D, Mohanta GP, Sudhakar M. Design and pharmacokinetic evaluation of ibrutinib by self-nano-emulsifying drug delivery system. Int J Pharm Sci Res. 2020;11(10):5254-61.
Nielsen FS, Petersen KB, Mullertz A. Bioavailability of probucol from lipid and surfactant based formulations in minipigs: influence of droplet size and dietary state. Eur J Pharm Biopharm. 2008;69(2):553-62. doi: 10.1016/j.ejpb.2007.12.020, PMID 18294829.
Gao P, Morozowich W. Development of supersaturatable self-emulsifying drug delivery system formulations for improving the oral absorption of poorly soluble drugs. Expert Opin Drug Deliv. 2006;3(1):97-110. doi: 10.1517/17425247.3.1.97, PMID 16370943.
Thomas N, Holm R, Mullertz A, Rades T. In vitro and in vivo performance of novel supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS). J Control Release. 2012 May 30;160(1):25-32. doi: 10.1016/j.jconrel.2012.02.027, PMID 22405903.
Craig D. An investigation into the mechanisms of self-emulsification using particle size analysis and low-frequency dielectric spectroscopy. Int J Pharm. 1995;114(1):103-10. doi: 10.1016/0378-5173(94)00222-Q.
Mamatha P, Arun Kumar J, Bhikshapathi DVRN. Design and optimization of ibrutinib solid lipid nanoparticles using design of experiment. IJBPAS. 2021;10(9):723-37.
Sokkula S, Gande S. Design and evaluation of self-nanoemulsifying drug delivery systems of manidipine for enhancement of solubility. Asian J Pharm Clin Res. 2019;288-295:10.22159.
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